We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Molecular Defects of Uroporphyrinogen Decarboxylase in a Patient with Mild Hepatoerythropoietic Porphyria.
- Authors
Meguro, Kuniaki; Fujita, Hiroyoshi; Ishida, Nobuhiro; Akagi, Reiko; Kurihara, Tatsuya; Galbraith, Richard A.; Kappas, Attallah; Zabriskie, John B.; Toback, Arnold C.; Harber, Leonard C.; Sassa, Shigeru
- Abstract
The molecular defect of uroporphyrinogen decarboxylase (UROD) was examined in a patient with mild hepato- erythropoietic porphyria. To elucidate the UROD defect, we cloned UROD cDNAs from EBV-transformed lympho- blastoid cells of the proband using reverse transcriptase-polymerase chain reaction. Nucleotide sequence analysis of the cloned UROD cDNAs revealed two separate missense mutations, each occurring in a separate allele. One mutation was a Val134 → Gin transition, and was due to three sequential point mutations (T417G418T419 → CCA); the other mutation was a His220 → Pro transition (A677→ C). UROD pheno- type studies demonstrated that the TGT → CCA mutation was inherited from the father, and the A → C mutation was inherited from the mother. In contrast to the null activity previously described for a mutant UROD from a patient with familial porphyria cutanea tarda, these mutant URODs had subnormal but substantial enzyme activities, when expressed in Chinese hamster ovary cells. This is the first demonstration of a mutation caused by three sequential base substitutions.
- Subjects
ENZYMES; PORPHYRIA; PATIENTS; POLYMERASE chain reaction; GENETIC mutation; NUCLEOTIDE sequence
- Publication
Journal of Investigative Dermatology, 1994, Vol 102, Issue 5, p681
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12374134